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TIGAR inclusion pathology is specific for Lewy body diseases.


Maximus Peto’s Commentary

This group reports a protein, TIGAR, co-localizes with alpha-synuclein in Lewy bodies, but not in multiple system atrophy.


TIGAR inclusion pathology is specific for Lewy body diseases.
Brain Res. 2019 Mar 1;1706:218-223.
López KLR, Simpson JE, Watson LC, Mortiboys H, Hautbergue GM, Bandmann O, Highley JR
DOI: 10.1016/j.brainres.2018.09.032
PubMed publication date (edat): 9/30/2018

Abstract

BACKGROUND:
We previously reported up-regulation of tigarb (the zebrafish orthologue of human TIGAR, TP53 – Induced Glycolysis and Apoptosis Regulator) in a zebrafish pink1-/- model of Parkinson’s disease (PD). Genetic inactivation of tigarb led to the rescue of dopaminergic neurons and mitochondrial function in pink-/- zebrafish. The aim of this study was to determine the relevance of TIGAR for human PD, investigate its disease specificity and identify relevant upstream and downstream mechanisms.

MATERIALS AND METHODS:
TIGAR Immunohistochemistry, using a range of antibodies, was undertaken for detailed assessment of TIGAR in formalin-fixed, paraffin-embedded tissue from post mortem brains of PD patients and other neurodegenerative disorders (n = 10 controls, 10 PD cases, 10 dementia with Lewy bodies, 5 motor neurone disease (MND), 3 multiple system atrophy (MSA)) and complemented by immunohistochemistry for p53, hexokinase I (HK-I) and hexokinase II (HK-II; n = 4 control, 4 PD, and 4 dementia with Lewy bodies).

RESULTS:
TIGAR was detected in Lewy bodies and Lewy neurites in the substantia nigra of sporadic PD and Dementia with Lewy bodies (DLB) patients. Staining of adjacent sections and double staining confirmed the presence of TIGAR alongside alpha-synuclein in these LB and neurites. In contrast, TIGAR-positive aggregates were not seen in cortical Lewy bodies. TIGAR protein was also absent in both TDP-43-positive inclusions in MND and glial cytoplasmic inclusions in MSA. Subsequent investigation of the TIGAR-upstream regulator p53 and the downstream targets HK-I and HK-II in PD brains suggested a possible mild increase in HK-I.

CONCLUSIONS:
TIGAR protein, is present in SN Lewy bodies of both sporadic PD and DLB. The absence of TIGAR protein in the pathological inclusions of MND or MSA suggests disease specificity and further raises the possibility that TIGAR may be involved in PD pathogenesis.

PMID: 30267647
Free Full-Text: http://eprints.whiterose.ac.uk/140251/1/Robles%20Lopez%20et%20al%20TIGAR%20and%20Lewy%20path%20for%20open%20access.pdf

Maximus Peto

Max Peto is a longevity researcher and founder of Long Life Labs. A biochemist by training, he studies the biochemistry of aging and longevity and has worked with research organizations such as SENS Research Foundation, Methuselah Foundation, BioAge Labs, Life Extension Foundation, and Ichor Therapeutics. His work at Long Life Labs is focused on empowering people to understand and manage the most critical factors for better health and longer life.

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